Sugar derivatives of nonsteroids having the effect of steroid hormones, and process of making the same



Patented Jan. 20, 1942 UNITEDQSTATES PATENT OFFICE azimsso SUGAR DERIVATIVES \OF :NONSTEROIDS HAVINGy-THE EFFECT- ,OF STEROID HOR- MONES, AND PROCESS OF MAKING THE SAME i q;

Karl Miescher, Riehen, and Werner Fischer and Jules Heer, Basel, Switzerland, assignors, by mesne assignments, to Ciba Pharmaceutical Products, Incorporated, Summit, N. J., a corporation of New Jersey No Drawing. Application February 21, 1939,;Se

rial No. 257,736. In Switzerland Mare! 16,

. 12 Claims. (Cl. 260-210) This invention relates to the manufacture of sides from phenols and'sugar acetates by zin new sugar derivatives of non-steroids having the chloride or para-toluene sulfohic m But effect of steriod hormones by treating such nonother known catalysts furthering the etherificasteroids with an etherifying sugar derivative in tion may also be used, for example silver oxide, the presence of a catalyst useful in furthering silver carbonate, mercury salts such as mercury etherification. H oxide, mercury acetate (cf. Berichtefvol. 62, As parent material there may be used any page 990 (1929) and mercury succinate, emulsion non-steroid, having the effect of steriod horand the glucosidase of yeast. mones, which contains at least one reactive hy- The new compounds may contain one or more droxyl group. The following compounds may be it) saccharide residues in the molecule and also hyp especially named as examples:alky1- or alkendroxyl groups which are still free or have been ylpoly-phenols such as 4:4-dioxy-o :,s"-diesterified or etherified. The saccharide residue ethyl-diphenylethane, 4:4 azp-tetroxy-aie-dimay also be present in the form of derivatives, ethyldiphenylethane, anol and dianols, hydroxy for instance in the form of their acylates.

compounds of the stilbene series such as The new compounds are characterized by their 4:4'-dioxystilbene, a:a-dialkyl-, -dialkenyl, -dibetter solubility in water and are useful in a1kinyl-, -a1kyl-aryl or -diary1-4:4-dio'xystiltherapeutics. i bene such as a:oU-dimethy1-4t4 dioxystilbene, The following example ill tr te t i 01.20: diethyl 4:4 dioxystilbene, u-methylation: ethyl-4:4-dioxystilbene, 002a diisopropyl 4:4'- 9 .1 part by weight of 4:4-dioxyeazp-diethylstil dioxystilbene, aloe diethinyl-4:4'-dioxystilbene bene', 3 parts Of.penta-acetylgluc s a d OJ part or a:u'diphenyl-4:4-dioxystilbene, further uof para-toluenesulfonic acid and '10 parts of benmono-a1ky1-, -alkenyl-, alkinylor -ary1-4:4'- Zene are boiled for five hours. Th solutionis dioxystilbene such as methyl-, ethyl-, ethenyl then taken up in benzene and washed with diethinyl-, allylor phenyl-4:4-dioxystilbenes. 5 lute caustic soda lye and water and then dried Further also oxy compounds of the olyphenylover sodium sulfate. After evaporating the benethane series which are substituted in ocand/or ene finally in a vacuum there is obtained t OU-pOsition by alkenyl, alkinyl or alkylides, such octaacetyl-bis-glucoside of dioxydiethylstilbene as for example 3:4-(4:4"-dioxy-dipheny1)2:4- 1n the form of colorless crystals. F. 227*230. hexadiene, 2:3-(4:4-di0xydiphenyl)-1:3-buta- It may be recrystallized from methanol or diene, onion diethinyl 4 :4 dioxy diphenylethanol.

ethane, u:a-dial1y1-2':2-dioxydiphenylethane, The acetyl derivative may be saponified by a-ethinyl 4z4" dioxy-diph-enyl thane, oz-etheheating a methanol solution thereof with 1 part ny1 2,findmhenmethane, ";4"' of a solution of 1 part of sodium in 100 parts of trioxy-triphenylethane. methanol for a short time. Water is then added,

Etherifying sugar derivatives include such Y Zf -bis (fi-g1ucoside)- ocZfi-diGthYlStllsugar derivatives as are capable of therifying belle 1S p tated in the form of a white powcompounds containing hydroxyl-groupsu Par- It y e recrystallized from butanol and ticular mention is made of the acyl compounds h dec mposition at about; 245, The and the acyloxy-halogen compounds of the 40 sapn1fi9at10n ay also be effected with other saccharides, such as for example acetyl glucose, Pydrollzlng agents, for example sodium hydroxpentacetyl glucose and acetobromo glucose. As

saccharides, there may be used for instance In analogous manner there may be bt mono-, dior tri-saccharides, such as glucosides, the 9 des of for instanc 4:4-bj -(p galactosides or galactose-glucosides. The proc- 414 f ess of the invention may be carried out by known g of same P t material.

methods in presence of a catalyst useful in 'fur- L t 8 Sam sacchandes can F ly W ll be obthering etherification, such as are described for ga by Way of other etherlfylng ugar derivaexample in Richter-Anschiitz, Chemie der Koh- Ives such as the correspondmg gen sugars or acetyl sugars even in presence of other lenstoffverbmdung 2, half- Page 359 catalysts furthering etherification, for instance (1935). This text-book describes for example zinc chloride, silver carbonate, mercury salts the action o hydrochlollc alcohohc sugar such as mercury acetate, mercury oxide and mersolutions, the reaction of alcohols with 1:2-oxides cury succinate, emulsion or the glucosidase or of sugars and the manufacture of phenolglycoyeast,

In quite similar manner the sugar derivatives of polyanols, for instance dianol, allq l-monoand poly-phenols, such as 4:4'-dioxy-a:;3-diethyl-diphenylethane, 4 4' oc ,o-tetroxy-a fi-diethyldiphenylethane, oxy-compounds of the polyphenylethane series which are substituted in 0:- and/or a'-position by alkenyl, alkinyl or alkylides, such as for example a:a-diethinyl-4':4"-dioxydiphenylethane, a-ethenyl 2'-oxy-dipheny1ethane, 0c ethy1idene-4z4 :4"-trioXy-triphenylethane, may be obtained.

What we claim is:

1. A process for the manufacture of glucoside derivatives comprising treating a non-steroid which is of phenol character and has the effect of steroid hormones and is a member of the group consisting of alkyland alkenylpolyphenols, with an etherifying derivative selected from the group consisting of the acyl and acyloxyhalogen compounds of the sacoharides, and with 20.

a catalyst useful in furthering etherification.

2. A process for a manufacture as claimed in claim 1, comprising treating the product thus obtained with hydrolizing agents.

3. A process for the manufacture of monosaccharide derivatives comprising treating a nonsteroid which is of phenol character and has the effect of steroid hormones and is a member of the group consisting of alkyl and alkenylpolyphenols, with an etherifying derivative selected from the group consisting of the acyl and acyloxy-halogen compounds of the saccharides, and with a catalyst useful in furthering etherification.

4. A process for the manufacture of glucoside derivatives of non-steroids having the effect of steroid hormones, comprising treating 4:4- dioxy-a2,8-diethy1-stilbene with an etherifying derivative selected from the group consisting of the acyl and acyloxy-halogen compounds of the saccharides, and with a catalyst useful in furthering etherification.

5. A process for the manufacture of glucoside derivatives of non-steroids having the effect of steroid hormones, comprising treating 4:4- dioxy-azp-diethyl-stilbene with a penta-acetylglucose and with a catalyst useful in furthering etherification.

6. A process for the manufacture of new glucoside derivatives of non-steroids having the effect of steroid hormones, comprising treating 014:4-dioXy-a:fl-diethyl-stilbene with a pentaacetylglucose and with para-toluenesulfonic acid.

7. A process for the manufacture of new glucoside derivatives of non-steroids having the effect of derivatives of non-steroids having the effect of steroid hormones, comprising treating 4:4- dioxy-a:fl-diethyl-stilbene with a penta-acetylglucose and with para-toluenesulfonic acid and then treating the product thus obtained with hydrolyzing agents.

8. A process for the manufacture of new glucoside derivatives of non-steroids having the effect of steroid hormones, comprising treating 4:4-dioxy-a:p-diethyl-stilbene with a pentaacetylglucose and with para-toluenesulfonic acid and then treating the product thus obtained with sodium ethylate.

9. The glucoside derivatives of non-steroids having the effect of steroid hormones and being members of the group consisting of alkyl and alkenyl-polyphenols.

10. The monosaccharide derivatives of nonsteroids having the effect of steroid hormones and being members of the group consisting of alkyland alkenyl polyphenols.

11. The monosaccharide derivatives of 4:4- diOXY-oz2/3-di6thYl-Sti1b8ll8.

12. Thefl-glucoside of 4:4'-dioXy-a:c-diethylstilbene melting with decomposition at 245 -C.

KARL MIESCHER. WERNER FISCHER. JULES HEER. 

